The proposed research may be considered in five categories: 1. Infection of the rat with the nematode, Nippostrongylus brasiliensis provides a model system for testing the role of IgE in host defense. To further define the self-cure reaction, it is proposed to evaluate the cell-mediated component of this reaction. Delayed hypersenstivity reactions to worm and larval antigens will be sought in vivo and the antigen-stimulated incorporation of H3-thymidine by spleen and mesenteric lymph node cells from infected rats tested in vitro. A migration inhibition assay will be developed and the effects of sensitized lymphocytes or their products on larvae and worms will be tested. 2. The process of sensitization for immediate hypersensitivity reactions involves the attachment of IgE antibodies to "receptors" on mast cells; addition of antigen leads to the release of mediators. It is proposed to investigate the modulating role of phospholipids on the release of mediators and the effect of cholera toxin on mast cells. In addition the possible "movement" of IgE antibodies, linked together by antigen, will be investigated and correlated with the release of histamine. 3. Infection with N. brasiliensis has been found to potentiate the IgE antibody response to conventional antigens in the rat. It is proposed to explore whether this influence is exerted on IgE producing cells in general, and whether potentiation is demonstrable in a second species, the mouse. 4. Indirect evidence suggests that migration of larvae through host tissues involves collagenolysis. It is proposed to define the properties of a collagenase-like enzyme of N. brasiliensis larvae and worms. 5. Oral and parenteral immunization with protein antigens was found to inhibit intestinal uptake of these macromolecules in vitro. It is proposed to explore the mechanism by which immunization interferes with absorption of proteins. The pathway of absorption of worm antigen will be explored and the effect of immunity to N. brasiliensis on antigen uptake assessed.